Method for producing alkyl-substituted butenols

ABSTRACT

Alkyl-substituted butenols having the formula (I):
 
R 1 —CH 2 —CH═CR 2 —CH 2 OH   (I)
 
wherein R 1  is a saturated or olefinically unsaturated alkyl or cycloalkyl group having from 4 to 16 carbon atoms and wherein R 1  is optionally substituted by an alkyl, cycloalkyl, aryl or alkaryl having up to 12 carbon atoms; R 2  is hydrogen or an alkyl group having from 1 to about 6 carbon atoms are produced by a process which comprises: (1) reacting an aldehyde of the formula (II):
 
R 1 —CH 2 —CHO   (II)
 
wherein R 1  has the same meaning as in formula (I), with the corresponding lower aldehyde to form an unsaturated aldehyde in an inert organic solvent; (2) continuously contacting an optionally calcined copper/zinc catalyst with the unsaturated aldehyde under isothermal conditions at temperatures of from about 45 to about 60° C. and under a hydrogen pressure of from 1 to about 300 bar.

BACKGROUND OF THE INVENTION

This invention relates to a process for the production ofalkyl-substituted butenols by reduction of the corresponding aldehydeprecursor in the presence of copper/zinc catalysts, the process beingcarried out continuously under isothermal conditions in a narrowtemperature range.

PRIOR ART

Judging by demand, the availability of many natural perfumes is totallyinadequate. From the perfumistic point of view, sandalwood oil is ratedparticularly highly and is of great value. It is obtained by steamdistillation from the heartwood of the sandalwood tree, a tropicalsemiparasite which occurs in India and Malaysia. Heartwood appears afterabout 10 years and only begins to develop relatively quickly in20-year-old trees. Fully grown trees are uprooted at the age of 30 to 60because the roots are particularly rich in fragrant heartwood [cf. E. T.Morris, Dragoco Report 1983 (30), 40]. It will therefore be appreciatedwhy perfume researchers are constantly endeavoring to develop suitablesubstitutes for natural sandalwood oil.

The focal points in the development of suitable substitutes for naturalsandalwood oil were outlined by R. E. Naipawer in a review [in: B. M.Lawrence, B. D. Mookherjee, B. J. Willis (Eds.): “Flavors andFragrances: A World Perspective”, Elsevier Publishers, Amsterdam 1988].In this review, it is mentioned inter alia that, since the middle of theseventies, campholenyl derivatives have played an important part assynthetic perfumes with a sandalwood perfume. A key role in this accessto synthetic sandalwood perfumes has been played by the fact thatcampholene aldehyde (B), the synthesis building block on which thecompounds mentioned are based, can readily be obtained from α-pinene, anatural substance.

2-Alkyl-4-(2,2,3-trimethylcyclopent-3-enyl)-but-2-en-1-ols (A),hereinafter referred to as sandalols, are sought-after perfumes with apronounced sandalwood fragrance.CY—CH₂—CH═CR—CH₂OH   (A)CY=4-(2,2,3-trimethylcyclopent-3en-1-yl) groupR=H or C₁₋₆ alkyl

JP-A2-55/036423 (reported in Chem. Abstr. 93/094886p) describes aprocess for the production of such a sandalol in which α-campholenealdehyde (B) is reacted with propionaldehyde (CH₃—CH₂—CHO) in thepresence of sodium hydroxide as basic catalyst.Cy—CH₂CHO   (B)Cy=4-(2,2,3-trimethylcyclopent-3-en-1-yl) group

The unsaturated aldehyde (C) formed in this mixed aldol condensation wasisolated in a yield of 73.5%.Cy—CH₂—CH═C(CH₃)—CHO (A)Cy=4(2,2,3-trimethylcyclopent-3-en-1-yl) group

Finally, in another step, this unsaturated aldehyde (C) was reduced withAl[OCH(CH₃)]₃ to form the corresponding sandalol (A). The yield obtainedis put at 85%.

DE-A-195 20 103 describes a process for the production ofalkyl-substituted butenols where unsaturated aldehydes are prepared byaldol condensation in a first step and are subsequently reduced in thepresence of an optionally calcined copper/zinc catalyst. Example 3 ofthis application (page 5, lines 5 to 26), which describes the secondstage of the process (reduction step), refers to batch operation and areaction temperature of 160° C.

Continuous operation in an extremely narrow and relatively lowtemperature range is neither disclosed nor suggested in DE-A-195 20 103.Isothermal operation is also not mentioned in DE-A-195 20 103.

DESCRIPTION OF THE INVENTION

The known processes for the production of sandalols (A) are not entirelysatisfactory in regard to yield and economy. Accordingly, there was aneed for an improved process for the production of the compounds (A) andanalogous compounds where the “Cy” group would be replaced by anothersaturated or olefinically unsaturated, optionally substituted alkyl orcycloalkyl group. More particularly, there was a need to ensure that thenonspecific formation of numerous secondary products would largely beavoided. Secondary products in a perfumistic context are understood tobe worthless or even troublesome products.

It has now been found that alkyl-substituted butenols corresponding togeneral formula (I):R¹—CH₂—CH═CR²—CH₂OH  (I)in which R¹ is a saturated or olefinically unsaturated alkyl orcycloalkyl group containing 4 to 16 carbon atoms which may optionally besubstituted by an alkyl, cycloalkyl, aryl or alkaryl group, with theproviso that this substituent contains at most 12 carbon atoms, and R²is hydrogen or an alkyl group containing 1 to 6 carbon atoms,can be produced in high yields providing the aldol condensation ofaldehydes corresponding to formula (II):R¹—CH₂—CHO  (II)in which R¹ has the same meaning as in formula (I), and thecorresponding lower aldehyde is carried out in an inert organic solventand the unsaturated aldehydes obtained are reduced in the presence of anoptionally calcined copper/zinc catalyst, the process being carried outcontinuously under isothermal conditions in a narrow temperature range.

Accordingly, the present invention relates to a process for theproduction of alkyl-substituted butenols corresponding to generalformula (II):R¹—CH₂—CH═CR²—CH₂OH  (I)in which R¹ is a saturated or olefinically unsaturated alkyl orcycloalkyl group containing 4 to 16 carbon atoms which may optionally besubstituted by an alkyl, cycloalkyl, aryl or alkaryl group, with theproviso that this substituent contains at most 12 carbon atoms, and R²is hydrogen or an alkyl group containing 1 to 6 carbon atoms,by reacting aldehydes corresponding to formula (II):R¹—CH₂—CHO  (II)in which R¹ has the same meaning as in formula (I), with thecorresponding lower aldehydes and subsequently reducing the unsaturatedaldehydes obtained,

-   i) the aldol condensation being carried out in an inert organic    solvent and-   (ii) the reduction of the unsaturated aldehydes being carried out in    the presence of an optionally calcined copper/zinc catalyst,    with the proviso that the reduction in step ii) is carried out    continuously under isothermal conditions at temperatures of 45 to    60° C. and under a hydrogen pressure of 1 to 300 bar.

The process according to the invention has the advantage over the priorart that intermediate products and valuable products are obtained inhigh purities and in substantially quantitative yields. In particular,it has the advantage that the valuable product (I) obtained in thehydrogenation step is formed with a very high chemical purity andselectivity. Of particular importance in this connection is the factthat unwanted secondary products, for example compounds derived from (I)of which the C═C double bonds are completely or partly hydrogenated, andunreacted aldehyde (from the aldol condensation), are formed in adistinctly reduced quantity by comparison with processes where thefeatures to be observed in accordance with the invention do not exist.This is particularly of advantage when the valuable product (I) obtainedin the hydrogenation step is used as a raw material for the productionof perfumes.

Step i)

Particularly suitable inert organic solvents for step i) are nonpolarsolvents which form an azeotrope with water. Examples of suitablesolvents are toluene, xylene, benzene, cyclohexane and methylcyclohexane.

In a special embodiment of the invention, ammonium salts of an organicacid are used to catalyze the aldol condensation.

Propionaldehyde is preferably used in a 2.5- to 10-fold molar excess,based on the aldehyde (II). In one particular embodiment,propionaldehyde is used in a 2.5- to 3.5-fold molar excess.

As already mentioned, the aldol condensation is preferably carried outin the presence of an ammonium salt of an organic acid in the processaccording to the invention. Basically, the nature of the acid is notcritical. Nor does it matter whether the ammonium salt is used as suchor whether it is formed in situ during the reaction—for example from anamine and an organic acid. Examples of suitable ammonium salts arebenzyl trimethyl ammonium hydroxide, piperidinyl acetate, pyrrolidiniumacetate, ammonium acetate, dimethyl ammonium pyridinyl acetate,morpholine acetate, Lewatit 11600 (active with acetic acid), piperidinylformate, N,N-tetraacetyl ethylenediamine, N,N-diacetyl ethylenediamine,dibutyl ammonium acetate and piperidinyl propionate. The concentrationof the catalyst is preferably in the range from 0.001 to 20 mole-% andmore particularly in the range from 0.5 to 10 mole-%, based on thealdehyde (II) used.

In another preferred embodiment of the present invention, R¹ in generalformula (I) is a 4-(2,2,3-trimethylcyclopent-3-enyl) group.

Step ii)

The process according to the invention is carried out at temperatures of45 to 60° C. In one particularly preferred embodiment, the reactiontemperature is in the range from 50 to 55° C.

The process according to the invention is distinguished inter alia bythe fact that, in step ii), it is carried out both continuously andisothermally.

Carrying out the process according to the invention continuously in stepii), which is preferably carried out in a fixed-bed reactor, ensuresthat the proportion of secondary products is small. The reason for thison the one hand is that, where this procedure is adopted, it is readilypossible by controlling the volumetric flow rate of aldehyde or aldehydeand solvent to keep the reaction time short. On the other hand, theheterogeneous catalysis applied here ensures that the reaction productis not accompanied by significant quantities of the catalyst.

Carrying out the process isothermally means that no significanttemperature gradients occur in the continuously operated reactor andthat, in particular, there are no temperature peaks. By contrast, anonisothermal reaction procedure would be characterized by theoccurrence of distinct temperature gradients or temperature peaks in thereactor. Nonisothermal conditions usually prevail in batchhydrogenation, i.e. hydrogenation in an autoclave. In continuousoperation, a nonisothermal reaction procedure would be characterized bythe absence of special precautions to control the exothermy of thereaction.

To establish isothermal conditions, a particular embodiment of theprocess according to the invention is characterized in that thetemperature is controlled by external jacket heating, for example withthermal oil, and/or the throughflow rate is adjusted to acorrespondingly high level.

In particular, the throughflow rate in step ii) is adjusted to a valueof 0.5 to 1.5 m³/h and more particularly to a value of 0.8 to 1.2 m³/h.

A preferred embodiment of the invention is characterized in that thecopper/zinc catalyst is used in particulate form, i.e. the catalystwhich is used in the reaction zone of the fixed-bed reactor is in theform of solid particles (heterogeneous catalyst). The particles mayassume various sizes and shapes, for example tablets, lumps, cylinders,rods, rings. Basically, the size of the particles is not critical.However, it is normally adapted to the particular reactor dimensionspresent so that the liquid phase and the carrier gas are able to passthrough the reaction zone unhindered and no unwanted drop in pressureoccurs in that region. Typical suitable particle sizes range from a meandiameter of ca. 1 millimeter to ca. 10 millimeters although larger orsmaller particle sizes are also possible.

A typical laboratory apparatus for carrying out the process according tothe invention comprises a fixed-bed reactor of a double-jacketed tube.The inner tube contains the heterogeneous hydrogenation catalyst andacts as the reaction zone. The intermediate space is used for heatingwith a liquid medium. The aldehyde or the mixture of aldehyde andsolvent can be delivered continuously to the reactor through heatablepipes by a controllable piston diaphragm pump. After leaving thereactor, the reaction products formed can readily be quantitativelyremoved via a cooling unit and an expansion system.

The typical technical equipment for carrying out the process accordingto the invention described with reference—by way of example—to alaboratory apparatus can readily be applied to correspondingly scaled uppilot-plant or production reactors. In principle, any of the usual tubeor tube-bundle reactors may be used for this purpose.

So far as the hydrogen pressure is concerned, step ii) of the process ispreferably carried out in the 200 to 300 bar range. Hydrogen pressuresof 220 to 260 bar are particularly preferred.

The hydrogenation in step ii) is preferably carried out in the presenceof a solvent. Alcoholic compounds, especially low molecular weightprimary alkanols, such as methanol and/or ethanol, are particularlysuitable solvents. The quantity ratio of aldehyde to solvent in step ii)of the process according to the invention is basically not criticalalthough ratios by volume of aldehyde to solvent of 10:1 to 1:10 arepreferred, a range of 3:1 to 1:1 being particularly preferred.

The copper/zinc catalysts to be used for the purposes of the inventionare known from the prior art. They are prepared in accordance withDE-A-42 42 466 by adding alkali metal carbonate compounds to aqueoussolutions containing water-soluble copper(II) and zinc(II) salts up to apH value of 6 to 10, removing and drying the deposit formed, calciningthe dried catalyst for 1 to 60 minutes at temperatures of 400 to 600° C.and then converting the calcined catalyst into particulate form. Furtherinformation on the production of the copper/zinc catalysts can be foundin DE-A-42 42 466, page 3, lines 13 to 34.

In order substantially to avoid further hydrogenation of the targetproduct (I) to secondary products, it has proved to be favorable in thecontinuous reaction in a fixed-bed reactor to adjust the volumetric flowrate of the aldehyde to LHSV values which are preferably in the rangefrom 0.3 to 3.0 h⁻¹ and more particularly in the range from 0.6 to 1.2h⁻¹. The LHSV value (liquid hourly space velocity) is understood fromthe literature to be the volumetric flow rate of the liquid, based onthe volume of the solid catalyst. The LHSV values mentioned herein arebased solely on the aldehyde, i.e. the solvent optionally used isdisregarded.

The circulating gas volume is adjusted to values of 1 to 2 Dm³/h(“pressure cubic meters per hour”). By circulating gas volume is meant:m³ circulating gas per hour for a reactor pressure of 250 to 300 bar.This parameter is measured in the pressure range of the reactor used(cf. Example 3 of the present application and the associated FIG. 1)after the gas circulation pump by means of a turbine.

For the purposes of the invention, the volumetric flow rate is normallyadjusted to GHSV values in the range from 200 to 1,000 h⁻¹ andpreferably to GHSV values in the range from 250 to 500 h⁻¹. The GHSVvalue (gaseous hourly space velocity) is understood from the literatureto be the volumetric flow rate of the carrier gas, based on the volumeof the solid catalyst.

EXAMPLES 1. Substances Used 1.1. For the Aldol Condensation

α-campholene aldehyde: 85% (Glidco)

propionaldehyde: 98% (Riedel-de-Häen)

KF on Al₂O₃: 240 g basic aluminium oxide were suspended in 320 g of a50% aqueous potassium fluoride solution and then concentrated to drynessin a water jet vacuum in a rotary evaporator. The catalyst was thendried for 4 hours at 130° C./50 mbar.

1.2. For the Reduction of the Unsaturated Aldehyde

Copper/zinc catalyst: The copper/zinc catalyst used was prepared inaccordance with Example A) of DE-A-42 42 466 using copper(II) nitratetrihydrate, zinc(II) nitrate hexahydrate and sodium carbonate.

2. The Reactions 2.1. Aldol Condensation Example 1

Quantities Used:

3.04 g (20 moles) α-campholene aldehyde

4.64 kg (80 moles) propionaldehyde

400 g basic aluminium oxide charged with 40% potassium fluoride.

Reaction Procedure:

1.5 kg of a mixture (molar ratio 1:4) of campholene aldehyde andpropionaldehyde was introduced into a 10-liter glass reactor. 400 kg ofKF on Al₂O₃ were added in portions under nitrogen (5 l/h) with vigorousstirring and cooling, the temperature of the reaction mixture being keptbetween 40 and 50° C. The remaining 6.2 kg of the aldehyde mixture werethen continuously added under nitrogen with vigorous stirring at a rateof 2 liters per hour. The reaction was exothermic and was kept bycooling at 40° C. After the addition, the mixture was stirred overnightat 50° C., the campholene aldehyde reacting off completely.

Working Up:

To remove the catalyst, the reaction mixture was pumped into a 2-literpressure nutsche and filtered under 5 bar nitrogen. The filter cake wasbriefly washed with 0.5 liter of isopropanol. The crude product wasreturned to the reactor and ca. 270 g organic phase and 22 g water phasewere distilled off at atmospheric pressure and at bottom temperatures ofup to 150° C. The residue of 5.1 kg left in the reaction vessel waswashed twice with 2 liters of saturated sodium sulfate solution. Theresidue of 5 kg remaining was further processed as a crude product (thecontent of 2-methyl-(2,2,3-trimethylcyclopent-3-en-1-yl)-but-2-en-1-alwas found by gas chromatography to be 43%).

Example 2

Quantities Used:

3.04 kg (20 moles) α-campholene aldehyde

2.9 kg (50 moles) propionaldehyde

170+85 g (3 moles) piperidine

120+60 g (3 moles) glacial acetic acid

2 kg toluene

Reaction Procedure:

3.04 kg of campholene aldehyde and 2 kg of toluene were introduced intoa 10-liter glass reactor and 2.9 kg of propionaldehyde, 170 g ofpiperidine and 120 g of glacial acetic acid were added with stirring atroom temperature. The mixture was then refluxed for 4 hours on a waterseparator, 680 ml of water of reaction being removed from the circuit.Analysis of a sample of the reaction mixture by gas chromatographyrevealed a percentage content of 15% of unreacted educt. Accordingly,another 85 g of piperidine and 60 g of glacial acetic acid were added.After refluxing for another hour, another 120 g of water were removedfrom the circuit and the educt was completely reacted.

Working Up:

After 1.9 kg of toluene had been distilled off, the reaction mixture waswashed twice with 2 liters of water. The organic phase of 6.24 kg wasdistilled in a 30 cm packed column (boiling point 88–102° C./0.1 mbar),3.27 kg of a yellowish colored product (gas-chromatographic purity 85%)being obtained (85% of the theoretical).

2.2. Reduction Example 3 Invention

Apparatus:

A jacketed high-pressure reactor filled with a Cu/Zn catalyst was used.It was connected to the following units: high-pressure product pump,heater, cooler, separator and gas circulation pump. The heat carriercircuit was controlled by a temperature-controllable apparatus. Thelayout of the apparatus used in schematized in FIG. 1.

LIST OF REFERENCE NUMERALS IN FIG. 1

-   1 educt (crude product of the aldol condensation of Example    2)/methanol-   2 high-pressure product pump-   3 heater-   4 reactor (jacketed)-   5 heat carrier oil-   6 cooler-   7 separator-   8 gas circulation pump-   9 hydrogen supply (“fresh H₂”)    Quantities Used:    24.7 kg crude product of the aldol condensation of Example 2    (=educt)    10.5 kg methanol, technical quality (=solvent)    26 kg Cu/Zn catalyst    Reaction Procedure:

After it had been filled with the catalyst, the reactor was closed andtested for leaks with 250 bar hydrogen pressure. The catalyst was thenactivated by continuous introduction of hydrogen under a reactorpressure of 50 bar N₂ and at a temperature increased by 5° C. per hour,a final temperature of 200° C. being established. The circulating gasvolume was kept at 1.5 Dm³/h. The end of activation of the catalyst, asreflected in an H₂ content in the circulating gas of more than 5%, i.e.the catalyst did not take up any more hydrogen, was followed by gasexchange in the reactor. To carry out the hydrogenation process, 250 barhydrogen was introduced into the reactor after the complete expansion ofhydrogen and the catalyst bed was adjusted to 50–55° C. through thehydrogen, reactor entry and heat carrier temperature. The circulatinggas volume was 2 Dm³/h. After the operating parameters had stabilized,the addition of a mixture of 2 parts by volume of the crude product ofthe aldol condensation of Example 2 (=educt) and 1 part by volume ofmethanol (=solvent) was started at 10 l/h, rising gradually to 40 l/h.After all the mixture had been added, the educt/hydrogen mixture showeda reactor entry temperature and heat carrier oil exit temperature of 55°C. The exothermy in the reactor was 5 to 10° C. After cooling, thehydrogenation product and the hydrogen were separated in a separator,the hydrogen was fed to the gas circulation pump and the end product wasremoved through an automatic expansion system. The crude productobtained in this way was then characterized by gas chromatography. Itcontained 86% of the required valuable product, 12% of a perfumisticallyattractive accompanying product and 1.8% of unreacted educt. Hardly anyof the secondary products formed, for example, at higher temperatures orin batch operation were detected.

1. A process for the production of an alkyl-substituted butenol havingthe formula (I):R¹—CH₂—CH═CR²—CH₂OH  (I) wherein R¹ is a saturated or olefinicallyunsaturated alkyl or cycloalkyl group having from 4 to 16 carbon atomsand wherein R¹ is optionally substituted by an alkyl, cycloalkyl, arylor alkaryl having up to 12 carbon atoms; and R² is hydrogen or an alkylgroup having from 1 to about 6 carbon atoms the process comprising: byreacting at least one aldehyde of the formula (II) with at least onecorresponding lower aldehyde:R¹—CH₂—CHO  (II) and R¹ has the same meaning as in formula (I); wherein:(i) aldol condensation is carried out in an inert organic solvent, and(ii) reduction of the unsaturated aldehydes is carried out in thepresence of an optionally calcined copper/zinc catalyst, and is carriedout continuously under isothermal conditions at a temperature rangingfrom 45 to 60° C. and under a hydrogen pressure of 1 to 300 bar at anLHSV (liquid hourly space velocity) of 0.3 to 3.0 hr⁻¹.
 2. The processof claim 1, wherein the aldol condensation is carried out in a nonpolarorganic solvent which can form an azeotrope with water.
 3. The processof claim 1, wherein the aldol condensation is carried out in thepresence of a catalyst which is an ammonium salt of an organic acid. 4.The process of claim 1, wherein R² in formula (I) is a methyl group. 5.The process of claim 1, wherein R² in formula (I) is a methyl group andwherein propionaldehyde is used in a 2.5 to 10-fold molar excess basedon the aldehyde of formula (II).
 6. The process of claim 5, wherein thepropionaldehyde is used in a 2.5 to 3.5-fold molar excess based on thealdehyde of formula (II).
 7. The process of claim 1 wherein R¹ is a4-(2,2,3-trimethylcyclopent-3-en-1-yl) group.
 8. The process of claim 1,wherein the organic solvent in (i) is selected from the group consistingof toluene, xylene, benzene, cyclohexane and methyl cyclohexane.
 9. Theprocess of claim 1, wherein R¹ is a saturated alkyl group having from 4to 16 carbon atoms.
 10. The process of claim 1, wherein R¹ is anolefinically unsaturated alkyl group having from 4 to 16 carbon atoms.11. The process of claim 1, wherein R¹ is an olefinically unsaturatedcycloalkyl group having from 4 to 16 carbon atoms.
 12. The process ofclaim 1, wherein R¹ is not further substituted.
 13. The process of claim1, wherein R¹ is substituted by an alkyl, cycloalkyl, aryl or alkarylhaving up to 12 carbon atoms.
 14. The process of claim 1, wherein R² ishydrogen.
 15. The process of claim 1, wherein R² is an alkyl grouphaving from 2 to 6 carbon atoms.
 16. The process of claim 1, whereinsaid LHSV (liquid hourly space velocity) ranges from 0.6 to 1.2 hr⁻¹.17. A process for the production of an alkyl-substituted butenol havingthe formula (I):R¹—CH₂—CH═CR²—CH₂OH  (I) wherein R¹ is a saturated or olefinicallyunsaturated alkyl or cycloalkyl group having from 4 to 16 carbon atomsand wherein R¹ is optionally substituted by an alkyl, cycloalkyl, arylor alkaryl having up to 12 carbon atoms; and R² is hydrogen or an alkylgroup having from 1 to about 6 carbon atoms the process comprising: byreacting at least one aldehyde of the formula (II) with at least onecorresponding lower aldehyde:R¹—CH₂—CHO  (II) and R¹ has the same meaning as in formula (I); wherein:(i) aldol condensation is carried out in an inert organic solvent, and(ii) reduction of the unsaturated aldehydes is carried out in thepresence of an optionally calcined copper/zinc catalyst, and is carriedout continuously in a fixed bed reactor at a LHSV (liquid hourly spacevelocity) of 0.3 to 3.0 hr⁻¹, under isothermal conditions at atemperature ranging from 45 to 60° C., and under a hydrogen pressure of1 to 300 bar.